While transcriptional controls can regulate expression of a gene, post-transcriptional mechanisms can also affect the ultimate level of gene expression by modulating the functional properties of the mRNA. These functional properties include the pre-mRNA processing, mRNA stability, mRNA translational efficiency, mRNA localization, mRNA sequestration, or mRNA editing and splicing (Izquierdo and Cueza, Mol. Cell Biol. 17: 5255–5268; Yang et al., J. Biol. Chem. 272: 15466–73, 1997; Ross, Microbiol. Rev. 59: 423–50, 1995). Post-transcriptional control mechanisms appear to play an especially important role in the gene expression response to environmental factors such as heat shock (Sierra et al., Mol. Biol. Rep. 19: 211–20, 1994), iron availability (Hentze et al., Proc. Natl. Acad. Sci. USA 93: 8175–82 (1996), oxygen (Levy et al., J. Biol. Chem. 271: 2746–53, 1996; McGary et al., J. Biol. Chem. 272: 8628–34, 1997), and growth factors (Amara et al., Nucleic Acids Res. 21: 4803–09, 1993).
The cis-elements that exert post-transcriptional regulatory effects on levels of protein ultimately present in a cell may be present in the 5′ and/or 3′ untranslated regions (UTRs) of the mRNA. At the 5′ UTR, mRNA binding to ribosomes is generally the rate-limiting step in the initiation of translation (Mathews et al., In: Translational Control, pages 1–30, Eds: Hershey et al., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1996). At the 3′ UTR, regulatory elements may modulate mRNA translation and degradation, as well as mRNA transport and subcellular localization (Jackson, Cell 74: 9–14, 1993).